Improved methods for repairing complex congenital heart defects in infancy have produced a dramatic increase in the population of adolescents and adult survivors. Emerging evidence suggests, however, that these patients are at increased risk of significant functional morbidities. Since 1988, we have followed a cohort enrolled in a prospective, randomized, single-center trial comparing the incidence of brain injury after use of two methods of vital organ support for repair of critical congenital heart disease in infancy. Our homogeneous study population is comprised of children with D-transposition of the great arteries (d-TGA) who underwent corrective surgery within the first 3 months of life. Multi-disciplinary assessments, conducted in the perioperative period and at ages 1, 4, and 8 years, included neurologic, developmental, speech, and MRI studies. Follow-up rates of 92% to 97% were achieved. These assessments revealed striking functional deficits that would be expected to place children at increased academic and mental health risk during adolescence. To characterize more fully any late effects of d-TGA and its repair, we propose to conduct additional evaluations of this unique study cohort at age 16 years, focusing on academic achievement, selected neuropsychological domains (attention, executive functions, memory, visual-spatial skills) and mental health status, including quality-of-life. Brain structure will be evaluated using quantitative volumetric MR segmentation and diffusion tensor imaging. A group of 50 age- and sex-matched control adolescents will be recruited for the structural MRI studies. Functional MRI studies will be conducted in 35 d-TGA and 15 control adolescents, and the activation maps in the two groups compared, using visual-spatial and verbal working memory tasks as probes. Clinical risk-stratification models will be developed for predicting late outcomes in children with d-TGA. Our collection of data prospectively from the time of surgical repair in infancy to adolescence would be unprecedented in the literature on congenital heart disease. [unreadable] [unreadable]